Guerin, O. | Search bioRxiv

bioRxiv2026

Vitality capacity preservation through lifelong aerobic exercise: a pathway to healthy ageing

BackgroundThe distinction between healthy and pathological ageing has led to the concept of vitality capacity (VC), which can be understood as the bodys physiological reserve. An individuals VC can be estimated using 12 biomarkers spread across 3 domains: immune and stress response, energy and metabolism and neuromuscular function. Vitality capacity may be preserved by lifelong physical activity. This cross-sectional study aimed to examine the relationship between lifelong aerobic physical activity and VC. MethodsVC of 20 lifelong active and 19 inactive healthy adults aged >55 years was assessed using 12 biomarkers across the three VC domains. Domain-specific z-scores were calculated and averaged to derive a global VC score. Principal component analysis was performed and loadings extracted to estimate domains weight, and multiple correlations were conducted to identify associations among biomarkers, domains and VC scores. ResultsVC was higher in lifelong active participants (+0.2 z-score units, p = 0.006) and correlated with age (r = -0.53, p < 0.001). Neuromuscular domain contributed most to VC variability, and the immune and stress response domain was higher in the active group (+0.4 z-score units, p = 0.001) as energy/metabolism among female participants (+0.5 z-score units, p.adj = 0.006). ConclusionLifelong aerobic physical activity is associated with higher VC in older adults, particularly within the immune and stress response domain. These findings highlight the role of physical activity in preserving the physiological reserve and reinforce the relevance of lifelong aerobic physical activity as a driver of healthy ageing.

physiology↗

bioRxiv2025

Fructose malabsorption induces dysbiosis and increases anxiety in Human and animal models

Background & AimsExcessive fructose intake is a growing public health concern, yet many individuals have a lower absorption capacity than the average intake, leading to widespread chronic fructose malabsorption. This results in intestinal fructose spillover, disrupting gut microbiota and triggering peripheral inflammation, which, along with neuroinflammation, plays a key role in mood disorders. This study investigates the connection between fructose malabsorption and mood disorders by examining gut microbiota changes in a human cohort and exploring their links with neuroinflammation in a GLUT5-KO mouse model. MethodsIn a human cohort, fructose malabsorption was assessed using a breath hydrogen test, while plasma lipopolysaccharide (LPS) levels and anxiety traits (measured using the State-Trait Anxiety Inventory, STAI) were analyzed. Gut microbiota composition was characterized through 16S rRNA sequencing, and dietary fructose intake was recorded. In the preclinical study, Glut5-KO mice, which lack intestinal fructose transport, were fed a 5% fructose diet for four weeks. Behavioral assays assessed anxiety- and depressive-like behaviors, while gut microbiota composition and microglia-associated gene expression were analyzed. ResultsAmong the recruited healthy volunteers, 60% exhibited fructose malabsorption, along with elevated plasma LPS levels, increased anxiety traits on the STAI, and distinct gut microbiota alterations, partially linked to fructose intake patterns. The average daily fructose intake was 30 g per individual, with significant variability in dietary sources. In the preclinical model, Glut5-KO mice on a 5% fructose diet displayed increased anxiety- and depressive-like behaviors, pronounced gut microbiota shifts, and altered expression of microglia-associated genes. ConclusionsThese findings highlight the complex interplay between dietary fructose, gut microbiota, and neuroinflammation in shaping mental health. Chronic fructose malabsorption may contribute to mood disorders through gut dysbiosis and microglia-dependent neuroinflammation, warranting further investigation into dietary interventions. HIGHLIGHTSO_LIFructose malabsorption is associated with anxiety traits in healthy volunteers. C_LIO_LIFructose malabsorption enhances anxiety-like behaviors in malabsorptive Glut5-KO mice. C_LIO_LIFructose malabsorption is associated with gut microbiota dysbiosis in human and preclinical mouse model of fructose malabsorption in association with fructose intake C_LIO_LIFructose malabsorption increases neuroinflammation and alters microglia functions in malabsorptive Glut5-KO mice. C_LI

microbiology↗